The contributions of host defense peptides in innate immunity and the shaping of the commensal flora are just beginning to be defined. Streptococcus mutans is a commensal within dental plaque that can attain cariogenic proportions when host dietary choices include significant amounts of sucrose. However, S. mutans strain variability is considerable at the DNA level and so it is reasonable to expect that strain variability in cariogenic potential also exists, including differing abilities to resist host immune mechanisms. This application proposes to test the hypothesis that S. mutans strains vary in their susceptibility patterns to host defense peptides. As a consequence we believe that the host-specific quantity and distribution of these peptides influences plaque colonization by particular S. mutans strains thereby helping to define overall caries risk. To test the hypothesis two specific aims are proposed. Aim 1 will examine S. mutans clones isolated from plaque samples obtained from caries-active and caries-free children and determine their susceptibility patterns to a panel of oral host defense peptides. Aim 2 will measure naturally occurring levels of host defense peptides in saliva samples corresponding to the saliva samples from Aim 1, and determine the levels of correlation between the distribution and quantity of host defense peptides, the susceptibility profiles of unique S. mutans genotypes, and the caries status of the children. The completion of this study will provide information regarding the potential contribution of host innate immunity, in the form of host defense peptides, to shape S. mutans colonization and therefore caries risk. This information will also be useful in assessing the potential efficacy of host defense peptides as therapeutic anti-caries agents. PUBLIC HEALTH RELEVANCE: This project will test the hypothesis that different strains Streptococcus mutans, the primary bacterial cause of dental caries, vary in their susceptibilities to host defense peptides. The hypothesis will be tested by assessing the levels of correlation between the distribution and quantity of host defense peptides, the susceptibility profiles of unique S. mutans genotypes, and the caries status of the children. The results will help determine the extent to which host innate immunity may influence colonization of dental plaque with particular strains of S. mutans and may therefore shape overall caries risk.